The objectives of this proposal are to understand the principles involved in the metabolic regulation of normal and sickle cell erythrocytes. Particular emphasis will be placed on the investigation of those enzymes responsible for the synthesis, degradation, and utilization of glycerate-2, 3-P2. The enzymes of special interest are: diphosphoglycerate mutase, diphosphoglycerate phosphatase, phosphoglycerate kinase, and monophosphoglycerate mutase. This study will include an evaluation of certain regulatory substances and intracellular environmental conditions which might ameliorate sickle cell anemia and, perhaps, other cardiovascular disorders.